The present application is related to Korean Patent Application No. 10-2001-0003956 (Jan. 27, 2001) entitled “NUCLEIC HYBRIDIZATION ASSAY METHOD AND DEVICE USING CLEAVAGE TECHNIQUE SPECIFICALLY RESPONSIVE TO SPECIFIC SEQUENCE OF COMPLEMENTARY DOUBLE BOND STRAND OF NUCLEIC ACID AND OLIGONUCLEOTIDE”; PCT Application No. PCT/KR02/00126 (Jan. 27, 2002) entitled “NUCLEIC HYBRIDIZATION ASSAY METHOD AND DEVICE USING A CLEAVAGE TECHNIQUE RESPONSIVE TO THE COMPLEMENTARY DOUBLE STRAND OR THE SINGLE STRAND OF NUCLEIC ACIDS OR OLIGONUCLEOTIDES”; Korean Patent Application No. 10-2001-0031284 (May 31, 2001) entitled “A MICRO VALVE APPARATUS USING MICRO BEAD AND METHOD FOR CONTROLLING THE SAME”; PCT Application No. PCT/KR02/01035 (May 31, 2002) entitled “A MICRO VALVE APPARATUS USING MICRO BEAD AND METHOD FOR CONTROLLING THE SAME”; Korean Patent Application No. 10-2002-0017558 (Mar. 27, 2002) entitled “BIO-DISK, BIO-DRIVER APPARATUS, AND ASSAY METHOD USING THE SAME”; Korean Patent Application No. 10-2005-0038765 entitled “DIGITAL BIO DISK (DBD), DBD DRIVER APPARATUS, AND ASSAY METHOD USING THE SAME”; and PCT Application No. PCT/KR2006/001709 entitled “DIGITAL BIO DISK (DBD), DBD DRIVER APPARATUS, AND ASSAY METHOD USING THE SAME”, the contents of all of which are incorporated herein for reference.
The efficiency and economy of most clinical diagnostic assay apparatuses for detecting a small amount of analyte in a fluid have been improved to date by designing apparatuses for preparing multiple samples and automatically adding reagents, as well as apparatuses for assaying a large number of test samples in parallel or in series. Such automated reagent preparation apparatuses and automated multiple-sample analyzers are frequently integrated into a single thin film apparatus. This thin film-type clinical experiment analyzer can accurately assay hundreds of analytes from a small amount of samples and reagents within one hour in an automatic or semi-automatic manner. However, such a thin film-type analyzer has a problem in that the complicated design of valves for controlling the flow and flow rate of samples or reagents (enzymes and buffer solutions) renders it difficult to make the analyzer a thin film.
In order to overcome this problem, there is a dire need to provide valves that are simple and adapted for thin films, and a thin film chemical analysis apparatus into which the valves are integrated.
CD and DVD as Thin Films
Standard CDs consist of a 12-cm polycarbonate substrate, a reflective metal layer, and a protective lacquer coating. Formats regarding CDs and DVDs follow ISO 9600.
The polycarbonate substrate is composed of transparent polycarbonate of an optical quality. In the case of CDs that have undergone standard printing or mass replication, the data layer is a part of the polycarbonate substrate, and the data is engraved as a series of pits by a stamper during the injection molding process. Particularly, polycarbonate is melted and injected into a mold at high pressure during the injection molding process. The polycarbonate is then cooled so that it has the mirror image of the mold, “stamper”, or “stamp”. The resulting pits on the disk substrate correspond to binary data, and are maintained by the polycarbonate substrate as the mirror image of the pits of the stamper created during the mastering process. The stamping master is commonly glass.
Such a disk can be adapted and modified into a thin film-type analysis apparatus for diagnosing and detecting a small amount of substance in a fluid (e.g. thin film chemical analysis apparatus). In this case, channels through which a fluid can flow, chambers for storing a buffer solution, holes, and valves may be formed on the disk surface during the injection molding process instead of pits.
As generally known in the art, conventional lab-on-a-chips have a plurality of chambers for storing a large amount of liquid-phase biological and chemical substances necessary for chemical processes. However, lab-on-a-chips cannot be commercialized until the following two problems are solved.
Firstly, the body of lab-on-a-chips repeats thermal expansion and contraction due to environmental factors (e.g. impact, temperature) during circulation and storage periods, even if the chambers are closed by physical valves. As a result, the valves have minute gaps, through which the liquid leaks out of the chambers due to the capillary phenomenon.
Secondly, although the liquid-phase substance must be stored in the chambers stably for a long period of time, the liquid itself is subjected to pressure resulting from evaporation and convection when the lab-on-a-chips are exposed to environmental factors (e.g. temperature) for a long period of time, and leaks out of the chambers through the minute gaps.
U.S. Patent Publication No. US005863708A discloses a valve using a temperature gradient caused by a biometallic material and a heated well. However, this valve has many problems regarding commercialization because it is difficult to control the valve by “heat control” without damaging the biomaterial, and because the liquid sealing problem due to evaporation and convection occurring inside the liquid cannot be overcome.
U.S. Pat. No. 6,063,589 entitled “DEVICES AND METHODS FOR USING CENTRIPETAL ACCELERATION TO DRIVE FLUID MOVEMENT ON A MICROFLUIDICS SYSTEM”, U.S. Pat. No. 5,186,844 entitled “APPARATUS AND METHOD FOR CONTINUOUS CENTRIFUGAL BLOOD CELL SEPARATION”, and U.S. Pat. No. 6,752,961 entitled “MODIFIED SIPHONS FOR IMPROVING METERING PRECISION” disclose capillary burst valves having chambers for gradually moving a liquid from the circular center in the outward direction while gradually increasing the rotation speed. Particularly, the disk is initially rotated at a low speed and then rotated at a higher speed so that the fluid moves to the next chamber. Such capillary burst valves have serious problems in that they are not applicable to a lab-on-a-chip process including centrifugation, which requires a high speed from the beginning, they can be opened only once, and they cannot be closed again after being opened.
Conventional valves, which have the above-mentioned two problems, cannot store a liquid in chambers for a long period of time. In an attempt to avoid such problems, U.S. Pat. No. 6,752,961 proposes that a separate diluent container be used to store a liquid and be broken just before the liquid inside the container is used. However, the fact that a bulky container must be stored inside the disk renders it impossible to make the disk a thin film.